Gentamicin is one of the aminoglycoside antibiotics which have their greatest utility in treating infections caused by gram-negative aerobic bacteria. (See, for example Barza et al., Am. J. Hosp. Pharm. 34: 723-737(July, 1977). While gentamicin is effective against most aerobic gram-negative bacteria, resistance is increasing and some strains of Proteus, Klebsiella, Serratia and Pseudomonas aeruginosa have become resistant to gentamicin therapy. (Barza et al., supra, p. 725).
Gentamicin sulfate (Garamycin) was the most widely prescribed parenteral aminoglycoside antibiotic in 1977, but the spread of gentamicin-resistant organisms has reduced its efficacy against gram negative bacilli. (Rahal, Jr., Current Prescribing, pp. 30-35 (August, 1977). Thus, while gentamicin is a valuable therapeutic tool in the fight against infections caused by aerobic gram-negative bacteria, the need for new gentamicin derivatives which exhibit activity against gentamicin-resistant strains has existed for several years.
Sagamicin is a structurally related aminoglycoside antibiotic which exhibits a similar anti-bacterial spectrum to that of gentamicin and further exhibits lower ototoxicity than does gentamicin.
The present invention provides new derivatives of gentamicin and sagamicin.